Your trachea, or windpipe, connects the throat and lungs. Air comes in through the windpipe; carbon dioxide goes out.
If it is torn or diseased, surgeons have two ways to fix it. They can remove the damaged part and attach the healthy ends, but there’s only so much slack. Or they can extract some rib cartilage and graft it into the windpipe, which is also made of cartilage. Additional surgery has risks, however. So some patients can’t be helped.
But what if doctors could grow you a new piece of windpipe, just the size and shape you need, from your own cartilage cells?
For the past year, the Feinstein Institute for Medical Research, in Manhasset, NY, has been exploring this question in collaboration with MakerBot.
The team of surgeons and scientists at the Feinstein Institute, the research branch of the North Shore-LIJ Health System, has grown cartilage on a scaffolding made from ordinary MakerBot PLA Filament. Their remarkable results, early investigations that might lead to a clinical breakthrough, are being presented today at the annual meeting of the Society of Thoracic Surgeons, in San Diego, CA.
Tissue Engineering + 3D Printing = New Possibilities
The Feinstein Institute’s findings build on innovations in two emerging fields: 3D printing and tissue engineering. Tissue engineering is like other kinds of engineering, except, instead of using steel or computer code to make things, living cells — skin, muscle, cartilage — are the raw material.
Researchers already know how to make cartilage from a mixture of cells called chondrocytes, nutrients to feed them, and collagen, which holds it all together. Shaping that cartilage into a nose or a windpipe is more challenging.
That’s where 3D printing comes in. The hope is to use a 3D printer to construct a scaffolding and cover it in a mixture of chondrocytes and collagen, which grows into cartilage. There are 3D printers that can extrude living cells, but options are few and expensive; one bioprinter cost $180,000 —beyond the Feinstein Institute’s budget.
So, at the end of 2013, Todd Goldstein, an investigator at the Feinstein Institute, called MakerBot. After several conversations, MakerBot agreed to provide the Feinstein Institute with two MakerBot Replicator 3D Printers, MakerBot PLA Filament, and expert advice in 3D modeling, 3D printing, and materials.
Real-Time Prototyping with Surgeons
Creating a replacement windpipe is uncharted medical territory. It has to be rigid enough to withstand coughs and sneezes, yet flexible enough to allow the neck to move freely.
To develop the scaffolding, Goldstein teamed up with two North Shore-LIJ surgeons who specialize in repairing windpipes. Goldstein would make prototypes of the scaffolding, then bring the prototypes to the surgeons to examine them. Goldstein would adjust his designs based on their feedback, and return in a day or two with an improved design.
Working this way, the Feinstein Institute team was able to develop a strong, flexible scaffolding design in less than a month. Goldstein, who had never used a 3D printer before his call to MakerBot, tested about 100 versions of the scaffolding. When he hit a design snag, he consulted with a designer at MakerBot, who analyzed the 3D files and suggested ways to optimize them for 3D printing.
“The ability to prototype, examine, touch, feel, and then redesign within minutes, within hours, allows for the creation of this type of technology,” says Dr. Lee Smith, a pediatric otolaryngologist at North Shore-LIJ who worked with Goldstein. “If we had to send out these designs to a commercial printer far away and get the designs back one and three and seven weeks later, we’d never be where we are today.”
“Without the 3D printers to do this, the amount of capital we would need would be exponential,” says Goldstein.
Experimenting with the MakerBot Replicator 2X
The next challenge the Feinstein Institute team faced was how to grow the cells on the scaffolding. To test the idea, Goldstein used a handheld syringe to apply the mixture of chondrocytes and collagen to the scaffolding. It was, he said, “like putting icing on a cake.”
After further consultation, MakerBot provided the Feinstein Institute with a MakerBot Replicator 2X Experimental 3D Printer, which has two extruders. Goldstein converted it into a low-cost bioprinter by replacing one extruder with a syringe that dispenses the chondrocyte-collagen “bio-ink.”
To mount the syringe on the MakerBot Replicator 2X, Goldstein modified a universal paste extruder that he found on Thingiverse. The paste extruder, which Thingiverse user nicksears remixed from other extruder parts, is in fact designed to put icing on a cake.
Goldstein modified the other extruder to print in PLA filament instead of ABS. “The advantage of PLA is that it’s used in all kinds of surgical implant devices,” says Dr. Smith, the pediatric surgeon. Goldstein found that the heat from the extruder head sterilizes the PLA as it prints, so he was able to use ordinary MakerBot PLA Filament.
The bio-ink, which stays at room temperature, fills the gaps in the PLA scaffolding, and then cures into a gel on the heated build plate of the MakerBot Replicator 2X. A two-inch-long section of windpipe (imagine a hollowed-out Tootsie Roll) takes less than two hours to print.
Once the bio-ink adheres to the scaffolding, it goes into a bioreactor, which will keep the cells warm and growing evenly. A new bioreactor costs between $50,000 and $150,000, so Goldstein found a broken incubator. With the help of an undergraduate intern, he is converting it into a bioreactor, with gears fabricated on a MakerBot Replicator 2 Desktop 3D Printer.
Proof of Concept
At the conference, Goldstein and Dr. David Zeltsman, the chief of thoracic surgery at Long Island Jewish Medical Center, are presenting the Feinstein Institute’s results from its investigations into how 3D printed windpipe segments held up for four weeks in an incubator. According to their abstract, “The cells survived the printing process, were able to continue dividing, and produce the extracellular matrix expected of tracheal chondrocytes.” In other words, they were growing like windpipe cartilage.
The Feinstein Institute is describing this work as a “proof of concept,” and the team still has plenty of work to do before establishing a new protocol for repairing or replacing damaged windpipes. Medical research can take years to move from bench to bedside, as can Food and Drug Administration approval.
Dr. Smith, the pediatric surgeon, says that he expects in the next five years to harvest a patient’s cells, grow them on a scaffolding, and repair a windpipe. At least one tracheal patient comes through the North Shore-LIJ Health System each year who can’t be helped by the two established methods. In such cases, the FDA has a compassionate therapy exception that allows you to try a promising experimental method like a 3D printed windpipe.
New Careers and The Future of Medicine
The windpipe experiment has already made a profound impact on the research team.
“It’s completely changed the trajectory of my academic career,” says Goldstein, who came to the Feinstein Institute as a molecular biologist, working with cells, chemicals, and drugs. Combining this knowledge with 3D printing and getting into tissue engineering — “I didn’t expect that at all when I got here.”
Now he is the Feinstein Institute’s lead researcher for 3D bioprinting, making models for pre-operative planning and tools to improve the lab. He is also the presenting author of a paper being delivered to thousands of surgeons, and is applying for major grants to continue his research. “Knowing that I could potentially have designed something that will end up saving someone’s child is the most exciting thing I could ever ask for,” Goldstein says.
“This project will probably define my scientific career,” says Dr. Smith. “As we produce something that can replace a segment of trachea, we’ll constantly be modifying and optimizing, the correct bio materials, the correct way to bond the cells to the scaffold.”
“3D printing and tissue engineering have the potential to replace lots of different parts of the human body,” he says. “The potential for creating replacement parts is almost limitless.”
So what’s next? MakerBot has supplied the Feinstein Institute with early samples of forthcoming MakerBot PLA Composite Filaments in Limestone and Iron, so the team can start investigating other applications of 3D printing and tissue engineering.
“Do you remember The Six Million Dollar Man?,” asks Daniel Grande, director of orthopedic research at the Feinstein Institute and Goldstein’s mentor. “The Bionic Man is not the future, it’s the present. We have that ability to do that now. It’s really exciting.”
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